4916
J. Org. Chem. 1997, 62, 4916-4920
Articles Reactions of Alcohols with Cesium Fluoroxysulfate Stojan Stavber,* Iztok Kosˇir, and Marko Zupan Laboratory for Organic and Bioorganic Chemistry, “Jozˇ ef Stefan” Institute and Department of Chemistry, University of Ljubljana, Jamova 39, 1000 Ljubljana, Slovenia Received December 30, 1996X
The reactions of alcohols with cesium fluoroxysulfate (CsSO4F) in MeCN suspension were studied, and the role of the structure of the alcohol and the reaction conditions on the course of reaction was determined. Secondary benzyl alcohols bearing a nonactivating aromatic ring were selectively oxidized to the corresponding ketones, while the CsSO4F-mediated reaction of phenyl-1-naphthylmethanol resulted in the formation of 1-fluoronaphthalene and benzaldehyde. Cyclic and noncyclic secondary alcohols were readily converted to ketones, as well as 1-hydroxybenzocyclanes to benzocyclanones-1, without any further fluorination or oxidation under the reaction conditions. On the other hand, reactions of primary alcohols with CsSO4F resulted in the formation of acid fluorides derived from further fluorination of aldehydes. Another type of transformation was observed in the case of alcohols bearing a benzyl functional group attached geminal to a hydroxy group, where decarbonylation of reactive intermediates resulting in the formation of benzyl fluoride derivatives became the main process. 2-Phenylethanol was so converted to benzyl fluoride and phenylacetyl fluoride in a 3:1 relative ratio, while 2-phenyl-1-propanol was selectively transformed to 1-phenyl-1-fluoroethane. The presence of the radical inhibitor nitrobenzene in the reaction mixture considerably inhibited conversion of the starting material. The same effect was observed by lowering the solvent polarity. Hammett correlation analysis of the effect of substituents on the reaction rates of oxidation of a set of substituted 1-phenyl-1-ethanols to acetophenones gave the reaction constant F+ ) -0.32, while analysis of analogous data for the transformations of benzyl alcohols to benzoyl fluorides gave the value of -0.54. A mechanism including radical intermediates was proposed for the transformation of alcohols by CsSO4F. Compounds possessing a fluoroxy moiety attract considerable interest among chemists. In spite of their usual high reactivity and moderate stability, fluoroxy compounds are often applied as useful reagents in organic synthesis. The chemistry of these compounds, used as selective fluorination reagents for organic molecules, was reviewed recently.1 Cesium fluoroxysulfate (CsSO4F) is the most stable and easily handled of them and, when some safety precautions are taken into account, can be conveniently used as a benchtop reagent. The organic chemistry of CsSO4F has been extensively studied during the last decade, leading to the recognition that its reactions with organic compounds strongly depend on the type of organic molecule and the functional groups present. The following types of reactions were observed: fluorofunctionalization of alkenes or alkynes through the addition or addition-elimination process, fluorosubstitution reactions at a saturated, unsaturated, or benzylic carbon atom and at a nitrogen atom, and oxidation or oxygenation of particular functional groups or heteroatoms. It was established that only small variations concerning the structure of the substrate or the reaction conditions are sufficient to change the reaction course drastically and favor one reaction type.1,2 Abstract published in Advance ACS Abstracts, June 1, 1997. (1) Rozen, S. Chem. Rev. 1996, 96, 1717. (2) (a) German, L., Zemskov, S., Eds. New Fluorinating Agents in Organic Syntheses; Springer-Verlag: Berlin, 1989. (b) Zupan, M.; Stavber, S. The Role of Reagent Structure in the Mild Introduction of a Fluorine Atom into Organic Molecules. In Trends in Organic Chemistry; Council of Scientific Information: Trivandrum, India, 1995; Vol. V, pp 11-36. X
S0022-3263(96)02424-3 CCC: $14.00
Scheme 1
Since, like all fluoroxy compounds, CsSO4F is also a strong oxidant,3 competition between fluorofunctionalization and oxidation of an organic molecule possessing oxidizable functional groups or heteroatoms can take place.4,5 In our continued interest in the organic chemistry of CsSO4F, we now report a more detailed study of its reactions with alcohols. Results and Discussion Role of the Structure of the Alcohol on the Course of Reaction. In a typical experiment, described in the Experimental Section, we treated diphenylmethanol (1a) with a 20% molar excess of CsSO4F in acetonitrile suspension and isolated benzophenone (2, Scheme 1) in almost quantitative yield, showing that the oxida(3) Steele, W. V.; O’Hare, P. A. G.; Appelman, E. H. Inorg. Chem. 1981, 20, 1022. (4) Stavber, S.; Zupan, M. Tetrahedron 1992, 48, 5875. (5) Stavber, S.; Kosˇir, I.; Zupan, M. J. Chem. Soc., Chem. Commun. 1992, 275.
© 1997 American Chemical Society
Reactions of Alcohols with Cesium Fluoroxysulfate Scheme 2
Scheme 3
tion of the benzylic hydroxy group is the exclusive process in this case. A different course of reaction was observed when phenyl(1-naphthyl)methanol (1b) reacted with CsSO4F under the same reaction conditions, and the fluorodealkylation process, resulting in 1-fluoronaphthalene (3) and benzaldehyde (4) as the reaction products, was found to be dominant in this case. We further studied the effect of substituents on the benzene ring in secondary benzylic alcohols on the course of the reaction with CsSO4F and found that the reaction is directed toward oxidation of the benzylic hydroxy group if the benzene ring is substituted with electron-withdrawing substituents (5a-6c, Scheme 2) and towards fluorodealkylation products when strong electron-donating groups are bonded para to the hydroxybenzyl block. Alkyl- and cycloalkyl-substituted benzyl alcohols (7, 8) were also readily transformed to the corresponding ketones, while R-(trifluoromethyl)benzyl alcohol (9) was found to be much more stable toward CsSO4F under the mentioned reaction conditions and converted to the ketone 14 in less than 50% yield. Cyclic alcohols (15, Scheme 3) were also readily converted to the corresponding ketones 16 with CsSO4F in MeCN medium. The resulting carbonyl products were
J. Org. Chem., Vol. 62, No. 15, 1997 4917 Scheme 4
found to be stable under the reaction conditions. No further fluorination to R-fluoro ketones, as observed with some N-F fluorinating reagents under similar reaction conditions,6 nor the Baeyer-Villiger type of oxidation, expected with reagents possessing similar oxidizing power,7 took place. Hydroxy-substituted benzocyclanes 17 were also selectively transformed to the corresponding benzocyclanones 18 and 1-phenyl-2-butanol (19a) to 1-phenyl-2-butanone (20a). No fluorofunctionalization of the benzylic carbon atom was observed in these cases, in spite of the fact that under the same reaction conditions benzocyclanes or alkyl-substituted aromatics could be effectively fluorinated at the benzylic position by CsSO4F.1,2b,8 2-Octanol (19b) was also quantitatively transformed to 2-octanone (20b), which was again stable under the reaction conditions. On the other hand, intermediate products derived from CsSO4F-mediated reactions with primary alcohols reacted further, and acid fluorides were isolated as the final result of the reactions, as shown in Scheme 4. Primary benzyl alcohols bearing a nonactivated benzene ring (21a-f) were transformed to the corresponding benzoyl fluorides (22), while strong donating substituents on the para position again favored the fluorodealkylation process. The primary formed aldehyde could be isolated only at short reaction times or a low CsSO4F/alcohol molar ratio. Thirty-five percent of benzaldehyde was detected in the crude reaction mixture after 10 min reaction of benzyl alcohol (21c) with an equimolar amount of CsSO4F, while the relative ratio of aldehyde rose to 85% when a 2-fold excess of starting alcohol was used. After the reaction times ordinarily needed for oxidation of secondary alcohols with an equimolar or excess amount of CsSO4F only benzoyl fluorides and the starting benzyl alcohols were detected in the reaction mixtures, thus indicating that the fluorination of aldehydes to acid fluorides9 is faster than the oxidation of primary alcohols to aldehydes. Furthermore, we established the role of the structure of a primary alcohol molecule on the reaction course. Alkyl-substituted primary alcohols (23, 24, Scheme 5) were selectively converted to acid fluorides (27, 28) in high yield, while a benzylic functional group attached geminal to the hydroxy interfered in the reaction pathway, causing the decarbonylation of reactive intermedi(6) Stavber, S.; Zupan, M. Tetrahedron Lett. 1996, 37, 3591. (7) Hudlicky´, M. Oxidations in Organic Chemistry; ACS Monographs 186; American Chemical Society: Washington, DC, 1990. (8) Stavber, S.; Zupan, M. J. Org. Chem. 1991, 56, 7347. (9) Stavber, S.; Planinsˇek, Z.; Zupan, M. J. Org. Chem. 1992, 57, 5334.
4918 J. Org. Chem., Vol. 62, No. 15, 1997
Stavber et al.
Scheme 5
Table 1. Effect of the Reaction Conditions on the Transformation of Acohols with CsSO4Fa substrate C6H5CH(Me)OH, 5b
solvent
MeCN MeCN/0.1 mmol PhNO2 MeCN/1 mmol PhNO2 CH2Cl2 m-CF3C6H4CH(Me)OH, 5d MeCN MeCN/0.1 mmol PhNO2 MeCN/1 mmol PhNO2 p-MeC6H4CH2OH, 21a MeCN MeCN/0.1 mmol PhNO2 MeCN/1 mmol PhNO2 MeCN/CH2Cl2 9:1 MeCN/CH2Cl2 4:1 MeCN/CH2Cl2 3:1 C6H5CH2OH, 21c MeCN MeCN/0.1 mmol PhNO2 MeCN/1 mmol PhNO2 MeCN/CH2Cl2 9:1 MeCN/CH2Cl2 4:1 MeCN/CH2Cl2 3:1 n-C6H14 C6H5CH(Me)CH2OH, 26 MeCN MeCN/0.1 PhNO2 MeCN/1 mmol PhNO2 MeCN/CH2Cl2 9:1 MeCN/CH2Cl2 8:1 MeCN/CH2Cl2 6:1
yieldb (%) 95; 10b 80 55 traces 93; 10d 86 59 98; 22a 42 18 69 54 traces 98; 22c 65 26 79 53 0 0 91; 31 30 traces 48 39 traces
a Standard reaction conditions: 1 mmol of substrate in 2 mL of solvent; inert atmosphere; 2.4 mmol (in the case of 5b and 5d 1.2 mmol) of CsSO4F; T ) 35 °C; 1 h. b Measured from 1H (10a, 10d) or 19F NMR spectra (22a, 22c, 31) of crude reaction mixtures using anisole or octafluoronaphthalene as internal standard; calculated on starting material.
ates and resulting in the formation of benzyl fluoride derivatives (30, 31). 2-Phenylethanol (25) was thus converted to benzyl fluoride (30) and phenylacetyl fluoride in a 3:1 relative ratio, while 2-phenyl-1-propanol (26) was selectively transformed to 1-phenyl-1-fluoroethane (31) and carbon monoxide, as detected by MS analysis of the evolved gas. Effect of Radical Scavenger and Solvent. The important role of the solvent and the presence of various radical scavengers in the reactions of CsSO4F with different types of organic molecules, pointed out in several previous reports1,2b, was also established in the reactions of CsSO4F with alcohols. Nitrobenzene, often used as a radical inhibitor, when added to the reaction mixture while keeping the other reaction parameters constant, reduced the conversion of 1-phenylethanol (5b) and its m-CF3 analogue (5d) to the corresponding acetophenone by up to 37% (Table 1). The transformation of benzyl alcohol (21c) or its p-Me derivative (21a) was suppressed by more than 80%, while the reaction of 2-phenyl-1-propanol (26) was completely inhibited by the presence of an equimolar amount of nitrobenzene. The degree of inhibition of the reaction caused by the presence of a radical scavenger is comparable to those determined
for the reactions of CsSO4F with aldehydes9 in the case of secondary alcohols, while in the case of benzyl alcohol and 2-phenyl-1-propanol the inhibition is twice as strong as for the reactions of CsSO4F with the corresponding aldehydes.9 The conversion of these primary alcohols to acid fluorides or benzyl fluorides, respectively, are also much more influenced by the solvent than the transformation of the analogous aldehydes to the same products,9 as is evident from the data in Table 1. Less than 25% of CH2Cl2 in the solvent mixture stopped the reaction in the case of 21a,c, and 15% was sufficient to obtain the same effect in the case of 26. Effect of the Structure of the Alcohol on Reaction Rates. Applying the competitive technique for determination of relative reactivities expressed by relative rate factors (krel),10 we established that benzyl alcohols are more reactive than alkyl-substituted derivatives. 1-Phenylethanol was found to be twice as reactive as 2-octanol (krel ) 1.8) and benzyl alcohol to the same degree more reactive than decanol (krel ) 1.7) or 2-phenyl-1-propanol (krel ) 2.1). This observation is in contrast to that found for the relative reactivities of the corresponding aldehydes in their reactions with CsSO4F, where the reactivity decreased in the order alkyl > aryl > benzyl substituted aldehyde.9 Correlation analysis using Hammett’s relations between reaction rates and substituent parameters afforded values of the reaction constant for the oxidation of a set of secondary (5) and primary (21) benzyl alcohols with CsSO4F. The Hammett correlation plot for the transformation of 1-phenylethanols (5a-g) to acetophenones, presented in Scheme 2, showed a satisfactory correlation of relative rate factors with σ+ substituent constants and gave a straight line with slope F+ ) -0.32 and a correlation coefficient of 0.97, while the analysis of analogous data for a set of benzyl alcohols (21a-f, Scheme 4) gave the value of -0.54 for the reaction constant and a correlation coefficient of 0.99. The reaction constant F+ for the oxidation of 5 to 10 has the same sign but lower magnitude than those reported for the same reaction using dimethyldioxirane (F ) -1.57),11 chromic acid (F ) -1.16),12 or chromium trioxide in acetic acid solvent (F ) -1.01)13 as oxidants and comparable to those for oxidation by chromium trioxide under basic (F ) -0.52) or neutral (F ) -0.37) conditions13 or by S2O82--CuII ( F ) -0.27).14 On the other hand, F+ for the CsSO4F-mediated conversion of 21 to 22 is considerably lower than those for the oxidation of benzyl alcohols to benzaldehydes by HNO3 (F ) -2.25)15 or HNO2 (F ) -1.70, Yukawa-Tsuno method)16 and comparable to those found for conversion of benzaldehydes to benzoyl fluorides (F+ ) -0.38)9 by CsSO4F. Proposed Mechanism. On the basis of the presented experimental results, the possible reaction pathways of transformation of secondary alcohols to ketones and primary alcohols to acid fluorides by CsSO4F are shown in Scheme 6. The electron-transfer process (A), resulting in the formation of cation radical intermediate 32, (10) Pearson, R. E.; Martin, J. J. Am. Chem. Soc. 1963, 85, 3142. (11) Kovae`, F.; Baumstark, A. L. Tetrahedron Lett. 1994, 35, 8751. (12) Lee, D. G.; Downey, W. L.; Maass, R. M. Can. J. Chem. 1968, 46, 441. (13) Kwart, H.; Francis, P. J. Am. Chem. Soc. 1955, 77, 4907. (14) Walling, C.; El-Taliawi, G. M.; Zhao, C. J. Org. Chem. 1983, 48, 4914. (15) Ogata, Y.; Sawaki, Y.; Matsunaga, F.; Tezuka, H. Tetrahedron, 1966, 22, 2655. (16) Moodie, R. B.; Richards, S. N. J. Chem., Soc. Perkin Trans. 2 1986, 1833.
Reactions of Alcohols with Cesium Fluoroxysulfate Scheme 6
followed by proton loss thus forming radical intermediate 33, which could also be obtained by direct hydrogen radical abstraction from the alcohol molecule (B), are two possible reaction pathways. In both cases, the processes can be mediated by SO4F- (path A1) or SO4•- (path A2). The electron-transfer process is generally accepted as the key reaction channel in the oxidation of organic molecules by peroxydisulfate where similar reactive species are involved, and in most cases the same reaction products are formed14,17 as in the present report. Since the fluoroxysulfate anion is an even stronger oxidant than peroxydisulfate18 and the ionization potentials of alcohols are between 9 and 10.5 eV, the electron-transfer pathway is the most probable process in these reactions, but direct hydrogen abstraction, suggested in some other oxidation reactions,11,19 could not be neglected. The electron deficiency in cation-radical intermediate 32 in the case of alkyl-substituted alcohols is located at the oxygen atom, while in the case of benzyl alcohols 32 is additionally stabilized due to resonance over the benzene ring.19 Proton loss, as the next step, can proceed from the hydroxy group, thus forming alkoxy radical 33a, or from the R-hydroxy carbon atom thus forming carbon radical (17) (a) Minischi, F.; Citterio, A.; Giordano, C. Acc. Chem. Res. 1983, 16, 27. (b) Walling, C.; Zhao, C.; El-Taliawi, G. M. J. Org. Chem. 1983, 48, 4910. (c) Walling, C.; El-Taliawi, G. M.; Amarnath, K. J. Am. Chem. Soc. 1984, 106, 7573. (18) The SO4F-/SO4H- couple has a standard electrode potential of 2.52 V3, and after F2, XeF2 and OF2 are the strongest oxidants among reagents used in organic synthesis, while the S2O82-/2SO42- couple has a standard electrode potential of 2.01 V.17a (19) Snook, M. E.; Hamilton, G. A. J. Am. Chem. Soc. 1974, 96, 860.
J. Org. Chem., Vol. 62, No. 15, 1997 4919 Table 2. Yields of Isolated Products in the Reactions of Alcohols with CsSO4F product
isolation method
yield(%)
benzophenone, 2 1-fluoronaphthalene, 3 3′-methylacetophenone, 10a acetophenone, 10b 4′-bromoacetophenone, 10c 3′-bromoacetophenone, 10d 3′-(trifluoromethyl)acetophenone, 10e 4′-(trifluoromethyl)acetophenone, 10f 4′-nitroacetophenone, 10g 3′-chlorobenzophenone, 11a 3′-(trifluoromethyl)benzophenone, 11b 4′-nitrobenzophenone, 11c propiophenone, 12 cyclopropylphenyl ketone, 13 R,R,R-trifluoroacetophenone, 14 cyclopentanone, 16a cyclohexanone, 16b cycloheptanone, 16c 1-indanone, 18a 1-tetralone, 18b 1-phenyl-2-butanone, 20a 2-octanone, 20b 4′-methylbenzoyl fluoride,9 22a 4′-fluorobenzoyl fluoride,9 22b benzoyl fluoride, 22c 4′-chlorobenzoyl fluoride,9 22d 4′-(trifluoromethyl)benzoyl fluoride,9 22e 3′-nitrobenzoyl fluoride,9 22f octanoyl fluoride,9 27 decanoyl fluoride,9 28 phenylacetyl fluoride,9 29 benzyl fluoride, 30 1-fluoro-1-phenylethane,9 31
CC TLC CC CC CC CC CC CC CC CC CC CC CC CC TLC GLC GLC GLC CC CC CC CC TLC GLC CC TLC GLC TLC GLC GLC GLC GLC TLC
92 48 93 90 89 89 88 85 83 88 87 82 91 94 44 59 62 64 85 86 87 87 76 49 76 78 46 74 50 50 10 32 78
33b, which after hydrogen radical abstraction is then transformed to the final carbonyl product. Both intermediates 33a,b were postulated and proved during peroxydisulfate-mediated oxidation of alcohols,14,17a,20 and it was suggested that the initially-formed alkoxy radical rapidly interconverts to the thermodynamically more stable carbon radical. It is interesting that according to our results disproportionation of cation-radical 32 or radical 33, regularly observed during peroxydisulfate oxidation of similar substrates, did not occur after CsSO4F-mediated oxidation. In this case, proton loss from 32 and hydrogen abstraction from 33 are probably considerably faster processes than disproportionation of the same intermediates.14,20b In the case of secondary alcohols, oxidation reactions stopped at the ketone formation step, while aldehydes, originally formed from primary alcohols, reacted further following the mechanism already proposed in our previous report,9 thus resulting in acid fluorides or benzyl fluorides. Definitive conclusions concerning the reaction pathway of oxidation of alcohols with CsSO4F cannot be given, but regarding the strong effect of the radical inhibitor on the reaction course and the magnitude of the reaction constant (F+), comparable to values obtained for many radical transformations of alcohols, the main intermediates involved in these reactions must be of a radical nature.
Experimental Section 1H
19F
and NMR spectra were recorded at 60 and 56.4 MHz, respectively. Alcohols from commercial sources were used. (20) (a) Ledwith, A.; Russell, P. J.; Sutcliff, L. H. J. Chem. Soc., Perkin Trans. 2 1973, 630. (b) Caronna, T.; Citterio, A.; Grossi, L.; Minischi, F.; Ogawa, K. Tetrahedron 1976, 32, 2741.
4920 J. Org. Chem., Vol. 62, No. 15, 1997 CsSO4F was prepared by the reaction of water solution of Cs2SO4 with F2 and handled according to the literature.21 Reactions of Alcohols with CsSO4F. General Procedure. A solution of 2 mmol of alcohol in 4 mL of freshly distilled and dry MeCN was degassed with argon. Then, 600 mg (2.4 mmol), or 1150 mg (4.6 mmol) in the case of primary alcohols, of CsSO4F was introduced, and the reaction suspension was stirred under Ar at 30-35 °C for 1 h. After dilution with 60 mL of CH2Cl2, the insoluble residue was filtered off, and the filtrate washed with saturated aqueous NaHCO3 (30 mL) and water (30 mL), dried (Na2SO4), and evaporated under reduced pressure. The crude reaction mixtures were analyzed by GLC and 1H and 19F NMR spectroscopy. The amounts of the products formed were determined from 1H or 19F NMR spectra of the crude reaction mixtures using anisole or octafluoronaphthalene as internal standards and yields calculated on starting material. Products were isolated by column chromatography (SiO2, n-hexane) or by preparative TLC (SiO2, n-hexane/CH2Cl2 4:1) or GLC (OV 101 10%, Chromosorb W A/W 80/100) and identified on the basis of the spectroscopic data and comparison with authentic samples or literature data. The yields collected in Table 2 refer to isolated pure products. (21) Appelman, E. H. Inorg. Synth. 1986, 24, 22.
Stavber et al. The Effect of Solvent on the Transformation of Alcohols. To a solution of 1 mmol of alcohol in 2 mL of solvent (CH2Cl2 or n-hexane), or a solvent mixture consisting of MeCN and CH2Cl2, degassed with argon, was added 300 mg (1.2 mmol) or 575 (2.3 mmol) of CsSO4F, and the reaction suspension was stirred under Ar at 35 °C for 2 h. The crude reaction mixtures were isolated and analyzed as cited in the General Procedure. The effect of the solvent on the course of reaction is presented in Table 1. The Effect of Radical Inhibitor on the Transformation of Alcohols. In a degassed solution of 1 mmol of alcohol in MeCN was introduced a corresponding amount of PhNO2 and CsSO4F (1.2 or 2.3 mmol) and the reaction suspension stirred at 35 °C under argon for 1 h. The crude reaction mixture was isolated and analyzed as cited and the effect on the transformation to carbonyl products presented in Table 1. Determination of Relative Rate Factors. The procedure already described in the literature was used.4,9
Acknowledgment. The financial support of the Ministry of Science and Technology of the Republic of Slovenia is gratefully acknowledged. JO962424A
